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Nature:牛津大学利用“蛋白探针”检测技术新应用

摘要 : 一种新的探测生物结构的方法或许将帮助治疗很多疾病,这一由牛津大学科学家们发明的方法,利用了化学手段将蛋白质聚集成“蛋白探针”,它们能被送入人体来检测多种疾病及炎症。结果发表在最新的《Nature》上。
一种新的探测生物结构的方法或许将帮助治疗很多疾病,这一由牛津大学科学家们发明的方法,利用了化学手段将蛋白质聚集成“蛋白探针”,它们能被送入人体来检测多种疾病及炎症。结果发表在最新的《Nature》上。 人体的免疫系统有自己的“蛋白探针”——抗体,抗体可以识别外来病原例如细菌和病毒,这些抗体有独特的形状以和目标的结构匹配,来形成“钥匙-锁”模型。早在1975年,科学家就试图用单克隆抗体来模拟这一过程,单克隆抗体目前广泛用于疫苗和生物技术领域。 牛津化学系的Ben Davis教授是项目负责人,他说:“天然抗体效果不总是那么好的,而我们的新型蛋白探针利用的是化学技术得到,因此能更精确的模拟天然蛋白结构,从而结合的效果更佳。”通过和目标细胞的蛋白质结合,例如慢性脑炎细胞,这些探针就会在组织中留下记号,而这些记号又可以通过显微镜或其它方法探测到。 文章中详细介绍了科学家是如何控制简单的氨基酸链模拟自然界的复杂结构的。将这一技术和已有的蛋白质模板结合就可以制造和测试针对特定生物结构的蛋白探针。在某些情况下,科学家发现这些蛋白探针和目标蛋白质结合的效果要比单克隆抗体更好。 Davis最后表示:“这些探针背后的技术对于研制医药等领域的合成蛋白是非常有帮助的。” 原文链接:Nature Expanding the diversity of chemical protein modification allows post-translational mimicry Sander I. van Kasteren, Holger B. Kramer, Henrik H. Jensen, Sandra J. Campbell, Joanna Kirkpatrick, Neil J. Oldham, Daniel C. Anthony, Benjamin G. Davis One of the most important current scientific paradoxes is the economy with which nature uses genes. In all higher animals studied, we have found many fewer genes than we would have previously expected. The functional outputs of the eventual products of genes seem to be far more complex than the more restricted blueprint. In higher organisms, the functions of many proteins are modulated by post-translational modifications (PTMs)1. These alterations of amino-acid side chains lead to higher structural and functional protein diversity and are, therefore, a leading contender for an explanation for this seeming incongruity. Natural protein production methods typically produce PTM mixtures within which function is difficult to dissect or control. Until now it has not been possible to access pure mimics of complex PTMs. Here we report a chemical tagging approach that enables the attachment of multiple modifications to bacterially expressed (bare) protein scaffolds: this approach allows reconstitution of functionally effective mimics of higher organism PTMs. By attaching appropriate modifications at suitable distances in the widely-used LacZ reporter enzyme scaffold, we created protein probes that included sensitive systems for detection of mammalian brain inflammation and disease. Through target synthesis of the desired modification, chemistry provides a structural precision and an ability to retool with a chosen PTM in a manner not available to other approaches. In this way, combining chemical control of PTM with readily available protein scaffolds provides a systematic platform for creating probes of protein–PTM interactions. We therefore anticipate that this ability to build model systems2 will allow some of this gene product complexity to be dissected, with the aim of eventually being able to completely duplicate the patterns of a particular protein’s PTMs from an in vivo assay into an in vitro system.     作者:Snail 点击:
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